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Rationale: The epidemiology and prognostic impact of increased pulmonary pressure among HIV-infected individuals in the antiretroviral therapy era is not well described., Objectives: To examine the prevalence, clinical features, and outcomes of increased echocardiographic pulmonary pressure in HIV-infected and -uninfected individuals., Methods: This study evaluated 8,296 veterans referred for echocardiography with reported pulmonary artery systolic pressure (PASP) estimates from the Veterans Aging Cohort study, an observational cohort of HIV-infected and -uninfected veterans matched by age, sex, race/ethnicity, and clinical site. The primary outcome was adjusted mortality by HIV status., Measurements and Main Results: PASP was reported in 2,831 HIV-infected and 5,465 HIV-uninfected veterans (follow-up [mean ± SD], 3.8 ± 2.6 yr). As compared with uninfected veterans, HIV-infected veterans with HIV viral load greater than 500 copies/ml (odds ratio, 1.27; 95% confidence interval [CI], 1.05-1.54) and those with CD4 cell count less than 200 cells/μl (odds ratio, 1.28; 95% CI, 1.02-1.60) had a higher prevalence of PASP greater than or equal to 40 mm Hg. As compared with uninfected veterans with a PASP less than 40 mm Hg, HIV-infected veterans with a PASP greater than or equal to 40 mm Hg had an increased risk of death (adjusted hazard ratio, 1.78; 95% CI, 1.57-2.01). This risk persisted even among participants without prevalent comorbidities (adjusted hazard ratio, 3.61; 95% CI, 2.17-6.01). The adjusted risk of mortality in HIV-infected veterans was higher at all PASP values than in uninfected veterans, including at values currently considered to be normal., Conclusions: HIV-infected people with high HIV viral loads or low CD4 cell counts have a higher prevalence of increased PASP than uninfected people. Mortality risk in HIV-infected veterans increases at lower values of PASP than previously recognized and is present even among those without prevalent comorbidities. These findings may inform clinical decision-making regarding screening and surveillance of pulmonary hypertension in HIV-infected individuals.

Rationale: It is not known whether the isolation of herpes simplex virus (HSV) from lower respiratory tract samples of nonimmunocompromised ventilated patients corresponds to bronchial contamination from the mouth and/or throat, local tracheobronchial excretion of HSV, or true HSV lung involvement (bronchopneumonitis) with its own morbidity/mortality., Objectives: This prospective, single-center, observational study was conducted to define the frequency, risk factors, and relevance of HSV bronchopneumonitis., Methods: All consecutive nonimmunocompromised patients receiving mechanical ventilation for 5 days or more were evaluated. Bronchoalveolar lavage, oropharyngeal swabs, and bronchial biopsies (presence of macroscopic bronchial lesions) were obtained for all who deteriorated clinically with suspected lung infection. HSV bronchopneumonitis was defined as this deterioration, associated with HSV in bronchoalveolar lavage and HSV-specific nuclear inclusions in cells recovered during lavage or bronchial biopsies., Measurements and Main Results: HSV bronchopneumonitis was diagnosed in 42 (21%) of the 201 patients who deteriorated clinically, with a mean mechanical ventilation duration before diagnosis of 14 +/- 6 days. Risk factors associated with HSV bronchopneumonitis were oral-labial lesions, HSV in the throat, and macroscopic bronchial lesions seen during bronchoscopy. Patients with HSV bronchopneumonitis were comparable to those without at admission, but their courses were more complicated, with longer duration of mechanical ventilation and intensive care unit stays., Conclusions: HSV bronchopneumonitis is common in nonimmunocompromised patients with prolonged mechanical ventilation, is associated with HSV reactivation or infection of the mouth and/or throat, and seems to be associated with poorer outcome.

We investigated the value of procalcitonin kinetics as a prognostic marker during ventilator-associated pneumonia (VAP). This prospective, observational study was conducted in a medical intensive care unit in a university hospital. All consecutive patients with microbiologically proven VAP who survived 3 days after its diagnosis were included and grouped according to clinical outcome: favorable or unfavorable, defined as death, VAP recurrence, or extrapulmonary infection requiring antibiotics before Day 28. Serum procalcitonin levels were measured on Days 1, 3, and 7 for all patients. Among the 63 patients included, 38 had unfavorable outcomes. On Day 1, they were more critically ill than patients with a favorable outcome. Serum procalcitonin levels decreased during the clinical course of VAP but were significantly higher from Day 1 to Day 7 in patients with unfavorable outcomes. Multivariate analyses retained serum procalcitonin levels on Days 1, 3, and 7 as strong predictors of unfavorable outcome. Based on these data, procalcitonin could be a prognostic marker of outcome during VAP.

The impact of methicillin resistance on morbidity and mortality of patients suffering from severe Staphylococcus aureus infections remains highly controversial. We analyzed a retrospective cohort of 97 patients with methicillin-susceptible and 74 patients with methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia (VAP). Initial empiric antibiotic therapy was appropriate for every patient. Patients with methicillin-resistant Staphylococcus aureus VAP were older, had higher disease-severity scores, and had been on mechanical ventilation longer at onset of VAP. Factors associated with 28-day mortality retained by multivariate logistic regression analysis were: age (odds ratio [OR] = 1.05, 95% confidence interval [CI], 1.02-1.08, p = 0.001) and Day 1 organ dysfunctions or infection (ODIN) score (OR = 1.90, 95% CI, 1.31-2.78, p = 0.001), but not methicillin resistance (OR = 1.72, 95% CI, 0.73-4.05, p = 0.22). The percentages of infection relapse or superinfection did not differ significantly between the two patient groups. In conclusion, after controlling for clinical and physiologic heterogeneity between groups, methicillin resistance did not significantly affect 28-day mortality of patients with Staphylococcus aureus VAP receiving appropriate antibiotics.

Results of routine microbiologic cultures of specimens obtained before the onset of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients might help to identify the causative microorganisms and thus to select effective initial antimicrobial therapy. To test this hypothesis, we prospectively studied 125 consecutive VAP episodes for which the causative microorganisms were determined using bronchoscopic techniques. Upon entry into the study, each patient's hospital chart was reviewed and culture results of all previously obtained microbiologic specimens were recorded (mean number +/- SD per patient, 45 +/- 38). A total of 220 microorganisms were cultured at significant concentrations (> or = 10(3)/10(4) colony-forming units [cfu]/ml) from bronchoscopic specimens and considered responsible for pneumonia. Of these 220 organisms, only 73 (33%) were recovered before VAP onset, sometimes from multiple sites in the same patient but mainly from prior respiratory secretion cultures (n = 53). Also previously isolated were 342 organisms that were not responsible for VAP, making prospective identifications of the true pathogens difficult. Among the 102 episodes for which prior respiratory secretion culture results had been obtained (mean time before VAP onset, 8 +/- 9 d), all the organisms ultimately responsible for pneumonia were previously recovered from only 36 (35%) of these specimens. Based on these data, the contribution of routine microbiologic specimens in guiding initial antimicrobial therapy decisions for patients with suspected VAP appears limited.

To describe the epidemiologic and microbial aspects of ventilator-associated pneumonia (VAP) in patients with acute respiratory distress syndrome (ARDS), we prospectively evaluated 243 consecutive patients who required mechanical ventilation (MV) for > or = 48 h, 56 of whom developed ARDS as defined by a Murray lung injury score > 2.5. We did this with bronchoscopic techniques when VAP was clinically suspected, before any modification of existing antimicrobial therapy. For all patients, the diagnosis of pneumonia was established on the basis of culture results of protected-specimen brush (PSB) (> or = 10(3) cfu/ml) and bronchoalvelolar lavage fluid (BALF) (> or = 10(4) cfu/ml) specimens, and direct examination of cells recovered by bronchoalveolar lavage (BAL) (< or = 5% of infected cells). Thirty-one (55%) of the 56 patients with ARDS developed VAP for a total of 41 episodes, as compared with only 53 (28%) of the 187 patients without ARDS for a total of 65 episodes (p = 0.0005). Only 10% of first episodes of VAP in patients with ARDS occurred before Day 7 of MV, as compared with 40% of the episodes in patients without ARDS (p = 0.005). All but two patients with ARDS who developed VAP had received antimicrobial treatment (mostly with broad-spectrum antibiotics) before the onset of infection, as compared with only 35 patients without ARDS (p = 0.004). The organisms most frequently isolated from patients with ARDS and VAP were methicillin-resistant Staphylococcus aureus (23%), nonfermenting gram-negative bacilli (21%), and Enterobacteriaceae (21%). These findings confirm that microbiologically provable VAP occurs far more often in patients with ARDS than in other ventilated patients. Because these patients are often treated with antibiotics early in the course of the syndrome, the onset of VAP is frequently delayed after the first week of MV, and is then caused mainly by methicillin-resistant S. aureus and other multiresistant microorganisms.

To determine risk factors for ventilator-associated pneumonia (VAP) caused by potentially drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and/or Stenotrophomonas maltophilia, 135 consecutive episodes of VAP observed in a single ICU over a 25-mo period were prospectively studied. For all patients, VAP was diagnosed based on results of bronchoscopic protected specimen brush (> or = 10(3) cfu/ml) and bronchoalveolar lavage (> or = 10(4) cfu/ml) specimens. Seventy-seven episodes were caused by "potentially resistant" bacteria and 58 episodes were caused by "other" organisms. According to logistic regression analysis, three variables among potential factors remained significant: duration of mechanical ventilation (MV) > or = 7 d (odds ratio [OR] = 6.0), prior antibiotic use (OR = 13.5), and prior use of broad-spectrum drugs (third-generation cephalosporin, fluoroquinolone, and/or imipenem) (OR = 4.1). Distribution of the 245 causative bacteria was analyzed according to four groups defined by prior duration of MV (< 7 or > or = 7 d) and prior use or lack of use (within 15 d) of antibiotics. Although 22 episodes of early-onset VAP in patients receiving no prior antibiotics were caused by antibiotic-susceptible bacteria, 84 episodes of late-onset VAP in patients receiving prior antibiotics were mainly caused by potentially resistant bacteria. Differences in the potential efficacies (ranging from 100% to 11%) against microorganisms of 15 antimicrobial regimens were studied according to classification into these four groups. These findings may provide a more rational basis for selecting the initial therapy of patients suspected of having VAP.

Although the pathogenesis of the acute respiratory distress syndrome (ARDS) is complex and poorly understood, several observations point to an important role of interactions between polymorphonuclear neutrophils (PMN) and cytokines in this process. We therefore studied certain parameters involved in PMN transendothelial migration (adhesion molecule expression and cytoskeletal organization) in patients with ARDS (n = 14) in comparison with other ventilated patients (n = 15). We found that in the basal state, both whole-blood PMN and alveolar PMN obtained by bronchoalveolar lavage (BAL) were activated, as shown by decreased L-selectin CD62L and increased beta 2 integrin CD11b expression, as well as decreased F-actin content. The degree of PMN activation increased with the degree of lung injury and with the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8). Moreover, the capacity of ex vivo stimulation of alveolar PMN by a bacterial peptide was low in ARDS and could partly account for the high susceptibility of these patients to lung infection. Therefore, ARDS-associated lung injury could be caused, at least in part, by inappropriate adhesion and transendothelial migration of proinflammatory cytokine-primed PMN.

To assess the reliability of quantitative cultures of endotracheal aspirates (EA) to diagnose ventilator-associated pneumonia, fiberoptic bronchoscopy was used to study 57 episodes of suspected lung infection in 39 patients with no recent changes in antimicrobial chemotherapy. A total of 19 cases (33%) of pneumonia were diagnosed based on the following criteria: protected specimen brush (PBS) sampling yielding > or = 10(3) cfu/ml of at least one microorganism and/or > or = 5% of cells containing intracellular bacteria on direct examination of bronchoalveolar lavage (BAL). The operating characteristics of EA cultures were calculated over a range of cutoff values (from 10(3) to 10(7) cfu/ml), and the threshold of 10(6) cfu/ml appeared to be the most accurate, with a sensitivity of 68% and a specificity of 84%. Microorganisms cultured from EA samples correlated weakly with those obtained using PSB specimens (rho = 0.32), with only 49 microorganisms among 123 (40%) found in both samples. These latter results and the relatively low sensitivity of the technique indicate that EA quantitative cultures are of limited value for the diagnosis of pneumonia in ventilated patients when fiberoptic techniques are available.

To compare the usefulness of specimens obtained by bronchoalveolar lavage (BAL) and using a protected specimen brush (PSB) in the diagnosis of nosocomial pneumonia, both procedures were performed via fiberoptic bronchoscopy just after death in a series of 20 ventilated patients who had not developed pneumonia before the terminal phase of their disease and who had no recent changes in antimicrobial therapy. These results were compared with both histologic and microbiologic postmortem lung features in the same area. The total number of bacteria obtained by culture of lung segments and the latters' histologic grade were closely correlated (rho = 0.79, p < 0.0001). PSB and BAL quantitative culture results were strongly correlated with lung tissue values (rho = 0.67 and 0.75, respectively; p < 0.0001). Using discriminative values of > or = 10(3) and > or = 10(4) bacteria/ml to define positive PSB and BAL cultures, respectively, these techniques identified lung segments yielding > or = 10(4) bacteria/g tissue with sensitivities of 82 and 91% and specificities of 89 and 78%, respectively. Moreover, upon direct observation, the percentage of BAL cells containing intracellular bacteria was closely correlated with the total number of bacteria obtained from corresponding lung samples (p < 0.001). These findings indicate that bronchoscopic PSB and BAL samples very reliably identify both qualitatively and quantitatively microorganisms present in lung segments with bacterial pneumonia, even when the infection develops as a superinfection in a patient already receiving antimicrobial treatment for several days.